NCT02718417 · CITED IN SOURCE DOCUMENTS

Avelumab in Previously Untreated Patients With Epithelial Ovarian Cancer (JAVELIN OVARIAN 100)

An NCI or FDA source cites this study. A citation does not establish that it applies to an individual diagnosis.

Phase: PHASE3
Status at capture: TERMINATED
Registry last update: 2020-07-14

This is a Phase 3, open-label, international, multi-center, efficacy, and safety study of avelumab in combination with and/or following platinum-based chemotherapy. Eligible patients must have previously untreated, histologically confirmed Stage III-IV epithelial ovarian (EOC), fallopian tube cancer (FTC), or primary peritoneal cancer (PPC) and be candidates for platinum-based chemotherapy. The primary purpose of the study is to demonstrate if avelumab given as single agent in the maintenance setting following frontline chemotherapy or in combination with carboplatin/paclitaxel is superior to platinum-based chemotherapy alone followed by observation in this population of newly diagnosed ovarian cancer patients.

Open the original ClinicalTrials.gov record → · Download preserved record

What did the study report?

Outcomes, safety and baseline populations are separate source sections. Quality-of-life measures appear under their original outcome titles.

flow

Participant flow

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baseline

Baseline characteristics

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outcome · POSTED

Progression-Free Survival (PFS) as Assessed by Blinded Independent Central Review (BICR)

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outcome · POSTED

Overall Survival

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outcome · POSTED

Progression-Free Survival (PFS) as Assessed by Investigator

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outcome · POSTED

Percentage of Participants With Objective Response as Assessed by Investigator

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outcome · POSTED

Percentage of Participants With Objective Response as Assessed by Blinded Independent Central Review (BICR)

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outcome · POSTED

Duration of Response (DOR) as Assessed by Investigator

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outcome · POSTED

Duration of Response (DOR) as Assessed by Blinded Independent Central Review (BICR)

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outcome · POSTED

Maintenance Progression-Free Survival as Assessed by Blinded Independent Central Review (BICR)

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outcome · POSTED

Maintenance Progression-Free Survival (PFS) as Assessed by Investigator

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outcome · POSTED

Percentage of Participants With Pathological Complete Response (pCR)

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outcome · POSTED

Progression-Free Survival 2 (PFS2)

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outcome · POSTED

Progression-Free Survival (PFS) as Assessed by Gynecological Cancer Intergroup (GCIG) Criteria

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outcome · POSTED

Number of Participants With Treatment-Emergent Adverse Events (AEs) Graded Based on, National Cancer Institute Common Terminology Criteria (NCI-CTCAE), Version 4.03

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outcome · POSTED

Number of Participants With Laboratory Abnormalities Greater Than or Equal to (>=) Grade 3, Based on National Cancer Institute Common Terminology Criteria (NCI-CTCAE), Version 4.03

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outcome · POSTED

Change From Baseline in Vital Signs - Blood Pressure at Day 1 of Cycles 2, 3, 4 in Chemotherapy Phase; Days 1, 15 and 29 of Cycles 1 and 2 in Maintenance/ Observation Phase and at End of Treatment

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outcome · POSTED

Change From Baseline in Vital Signs - Pulse Rate at Day 1 of Cycles 2, 3, 4 in Chemotherapy Phase; Days 1, 15 and 29 of Cycles 1 and 2 in Maintenance/ Observation Phase and at End of Treatment

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outcome · POSTED

Number of Participants With Electrocardiogram (ECG) Abnormalities

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outcome · POSTED

Functional Assessment of Ovarian Symptom Index- 18 (FOSI-18) Score

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outcome · POSTED

European Quality of Life-5 Dimensions-5 Levels (EQ-5D-5L) Score

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outcome · POSTED

Chemotherapy Phase: Maximum Plasma Concentration (Cmax) of Paclitaxel (Once a Week [QW] Regimen)

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outcome · POSTED

Chemotherapy Phase: Maximum Plasma Concentration (Cmax) of Paclitaxel (Once Every Three Weeks [Q3W] Regimen)

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outcome · POSTED

Chemotherapy Phase: Maximum Plasma Concentration (Cmax) of Carboplatin (Total and Free)

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outcome · POSTED

Chemotherapy Phase: Area Under the Plasma Concentration Time Curve From Time Zero to Infinite Time (AUCinf) of Paclitaxel (QW Regimen)

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outcome · POSTED

Chemotherapy Phase: Area Under the Plasma Concentration Time Curve From Time Zero to Infinite Time (AUCinf) of Paclitaxel (Q3W Regimen)

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outcome · POSTED

Chemotherapy Phase: Area Under the Plasma Concentration Time Curve From Time Zero to Infinite Time (AUCinf) of Carboplatin (Total and Free)

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outcome · POSTED

Chemotherapy Phase: Area Under the Concentration Time Curve From Time Zero to 24 Hours (AUC24) of Paclitaxel (QW Regimen)

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outcome · POSTED

Chemotherapy Phase: Area Under the Concentration Time Curve From Time Zero to 24 Hours (AUC24) of Paclitaxel (Q3W Regimen)

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outcome · POSTED

Chemotherapy Phase: Area Under the Concentration Time Curve From Time Zero to 24 Hours (AUC24) of Carboplatin (Total and Free)

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outcome · POSTED

Maintenance Phase: Predose Plasma Concentration (Ctrough) of Avelumab

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outcome · POSTED

Maintenance Phase: Maximum Plasma Concentration (Cmax) of Avelumab

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outcome · POSTED

Chemotherapy Phase: Maximum Plasma Concentration (Cmax) of Avelumab When Given With Paclitaxel and Carboplatin

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outcome · POSTED

Chemotherapy Phase: Predose Plasma Concentration (Ctrough) of Avelumab When Given With Paclitaxel and Carboplatin

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outcome · POSTED

Number of Participants With Anti-Drug Antibodies (ADA) Against Avelumab by Never and Ever Positive Status

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outcome · POSTED

Number of Participants With Neutralizing Antibodies (nAb) Against Avelumab by Never and Ever Positive Status

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outcome · POSTED

Number of Participants With Positive Programmed Death Receptor-1 Ligand-1 (PD-L1) Biomarker Expression in Tumor Tissue as Assessed by Immunohistochemistry (IHC)

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outcome · POSTED

Number of Participants With Positive Tumor-Infiltrating Cluster of Differentiation 8 (CD8+) T Lymphocytes Expression in Tumor Tissue as Assessed by Immunohistochemistry (IHC)

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adverse events

Adverse events

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more info

Limitations, agreements, and source contact

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Who could take part

eligibility Criteria: Key Inclusion Criteria: * Histologically confirmed Stage III-IV epithelial ovarian, fallopian tube, or primary peritoneal cancer, including malignant mixed Müllerian tumors with high grade serous component * Patients must be candidates for platinum based chemotherapy and previously untreated * Patients must have completed a surgical debulking procedure, or be candidates for neoadjuvant chemotherapy * Availability of an archival formalin fixed, paraffin embedded (FFPE) tumor tissue block or a minimum of 15 slides * ECOG PS 0-1 * Adequate hematological, renal, and liver function Key Exclusion Criteria: * Non epithelial tumors or ovarian tumors with low malignant potential (ie, borderline tumors) or mucinous tumors * Prior systemic anti-cancer treatment for EOC, FTC, or PPC including prior immunotherapy with IL 2, IFN α, or anti PD 1, anti PD L1, anti PD L2, anti CD137, or anti cytotoxic T lymphocyte associated antigen 4 (anti CTLA 4) antibody (including ipilimumab), or any other antibody or drug specifically targeting T cell co stimulation or immune checkpoint pathways * Patients for whom, in the opinion of the Investigator, there is clinical benefit to administer bevacizumab as a first-line treatment and for whom bevacizumab is approved and available in this setting. * Cancer for which intraperitoneal cytotoxic chemotherapy is planned * Active autoimmune disease (some exceptions include diabetes type I, vitiligo, psoriasis, hypo- or hyperthyroidism not requiring immunosuppressive treatment)
gender Based: true
healthy Volunteers: false
minimum Age: 18 Years
sex: FEMALE
std Ages: ADULT
OLDER_ADULT

Treatment arms and interventions

arm Groups

description
Chemotherapy followed by observation
intervention Names
Drug: carboplatin
Drug: paclitaxel
label
Arm A
type
ACTIVE_COMPARATOR
description
Chemotherapy followed by avelumab in maintenance
intervention Names
Drug: carboplatin
Drug: paclitaxel
Drug: Avelumab
label
Arm B
type
EXPERIMENTAL
description
Chemotherapy in combination with avelumab followed by avelumab in maintenance
intervention Names
Drug: carboplatin
Drug: paclitaxel
Drug: Avelumab
label
Arm C
type
EXPERIMENTAL

interventions

arm Group Labels
Arm A
Arm B
Arm C
description
Given Q3W during chemotherapy phase
name
carboplatin
type
DRUG
arm Group Labels
Arm A
Arm B
Arm C
description
Investigator choice of weekly or Q3W during chemotherapy phase
name
paclitaxel
type
DRUG
arm Group Labels
Arm C
description
Given Q3W in combination with carboplatin/paclitaxel during chemotherapy portion
name
Avelumab
type
DRUG
arm Group Labels
Arm B
Arm C
description
Given as single agent in maintenance portion Q2W
name
Avelumab
type
DRUG

Study design

allocation

RANDOMIZED

intervention Model

PARALLEL

masking Info

masking: NONE

primary Purpose

TREATMENT

Enrollment

count: 998
type: ACTUAL

Registered outcome plans (not posted results)

primary Outcomes

description
BICR assessed PFS: Duration from randomization until disease progression or death. PFS data was censored on the date of the last adequate tumor assessment for participants who did not have an event (progression of disease or death), who started a new anti-cancer therapy prior to an event or for participants with an event after 2 or more missing tumor assessments. Progression as per Response Evaluation Criteria in Solid Tumors (RECIST) version 1.1: as at least a 20 percent (%) increase in the sum of diameters of target lesions, taking as reference the smallest sum on study (this includes the baseline sum if that is the smallest on study). In addition to the relative increase of 20%, the sum must have also demonstrated an absolute increase of at least 5 millimeters (mm). The appearance of one or more new lesions was also considered progression. Analysis was performed using Kaplan-Meier method.
measure
Progression-Free Survival (PFS) as Assessed by Blinded Independent Central Review (BICR)
time Frame
Baseline to progression of disease or discontinuation from the study or death, whichever occurred first (maximum duration of 27 months)

secondary Outcomes

description
Overall survival was defined as the time (in months) from the date of randomization to the date of death due to any cause. Participants last known to be alive were censored at date of last contact. Analysis was performed using Kaplan-Meier method.
measure
Overall Survival
time Frame
Baseline to discontinuation from the study or death, whichever occurred first (maximum duration of 27 months)
description
Investigator assessed PFS was defined as time (in months) from date of randomization to the first documentation of disease progression or death (due to any cause), whichever occurred first. Progression as per RECIST 1.1, was defined as at least a 20% increase in the sum of diameters of target lesions, taking as reference the smallest sum on study (this includes the baseline sum if that is the smallest on study). In addition to the relative increase of 20%, the sum must have also demonstrated an absolute increase of at least 5 mm. The appearance of one or more new lesions was also considered progression. Analysis was performed using a Cox's Proportional Hazard model stratified by the randomization strata and a stratified log-rank test.
measure
Progression-Free Survival (PFS) as Assessed by Investigator
time Frame
Baseline to progression of disease or discontinuation from the study or death, whichever occurred first (maximum duration of 27 months)
description
Investigator assessed objective response according to RECIST version 1.1, was defined as participants with confirmed best overall response of complete response (CR) or partial response (PR). CR was defined as disappearance of all target and non-target lesions, and sustained for at least 4 weeks. Any pathological lymph nodes (whether target or non-target) must have reduction in short axis to less than (\<) 10 mm. PR was defined as at least 30% decrease in the sum of the longest dimensions of target lesions taking as reference the baseline sum longest dimensions.
measure
Percentage of Participants With Objective Response as Assessed by Investigator
time Frame
Baseline to progression of disease, start of new anti-cancer therapy or discontinuation from study or death, whichever occurred first (maximum duration of 27 months)
description
BICR assessed objective response according to RECIST version 1.1, was defined as participants with confirmed best overall response of CR or PR. CR was defined as disappearance of all target and non-target lesions, and sustained for at least 4 weeks. Any pathological lymph nodes (whether target or non-target) must have reduction in short axis to \<10 mm. PR was defined as at least 30% decrease in the sum of the longest dimensions of target lesions taking as reference the baseline sum longest dimensions.
measure
Percentage of Participants With Objective Response as Assessed by Blinded Independent Central Review (BICR)
time Frame
Baseline to progression of disease, start of new anti-cancer therapy or discontinuation from study or death, whichever occurred first (maximum duration of 27 months)
description
Investigator assessed DOR: time (in months) from the first documentation of objective response (confirmed CR or PR) to the date of first documentation of PD or death due to any cause. As per RECIST version 1.1, CR was defined as disappearance of all target and non-target lesions, and sustained for at least 4 weeks. Any pathological lymph nodes (target or non-target) must have reduction in short axis to \<10 mm. PR: at least 30% decrease in the sum of the longest dimensions of target lesions taking as reference the baseline sum longest dimensions. PD was defined as at least a 20% increase in the sum of diameters of target lesions, taking as reference the smallest sum on study (this included the baseline sum if that is the smallest on study). In addition to the relative increase of 20%, the sum must have also demonstrated an absolute increase of at least 5 mm. The appearance of one or more new lesions was also considered progression. Analysis was performed using Kaplan-Meier method.
measure
Duration of Response (DOR) as Assessed by Investigator
time Frame
First response subsequently confirmed to progression of disease or start of new anti-cancer therapy or discontinuation from the study or death, whichever occurred first (maximum duration of 27 months)
description
BICR assessed DOR: time (in months) from the first documentation of objective response (confirmed CR or PR) to the date of first documentation of PD or death due to any cause. As per RECIST version 1.1, CR was defined as disappearance of all target and non-target lesions, and sustained for at least 4 weeks. Any pathological lymph nodes (target or non-target) must have reduction in short axis to \<10 mm. PR: at least 30% decrease in the sum of the longest dimensions of target lesions taking as reference the baseline sum longest dimensions. PD was defined as at least a 20% increase in the sum of diameters of target lesions, taking as reference the smallest sum on study (this included the baseline sum if that is the smallest on study). In addition to the relative increase of 20%, the sum must have also demonstrated an absolute increase of at least 5 mm. The appearance of one or more new lesions was also considered progression. Analysis was performed using Kaplan-Meier method.
measure
Duration of Response (DOR) as Assessed by Blinded Independent Central Review (BICR)
time Frame
First response subsequently confirmed to progression of disease or start of new anti-cancer therapy or discontinuation from the study or death, whichever occurred first (maximum duration of 27 months)
description
BICR assessed maintenance PFS was defined as the time from Cycle 1 Day 1 of the maintenance phase to the date of the first documentation of PD or death due to any cause, whichever occurs first. It was defined, for participants who proceeded to maintenance phase and who did not have disease progression by BICR during the chemotherapy phase. As per RECIST version 1.1, PD was defined as at least a 20% increase in the sum of diameters of target lesions, taking as reference the smallest sum on study (this included the baseline sum if that is the smallest on study). In addition to the relative increase of 20%, the sum must have also demonstrated an absolute increase of at least 5 mm. The appearance of one or more new lesions was also considered progression. Analysis was performed using Kaplan-Meier method.
measure
Maintenance Progression-Free Survival as Assessed by Blinded Independent Central Review (BICR)
time Frame
From Day 1 of Cycle 1 (42 days) of maintenance phase to progression of disease or death, whichever occurred first (maximum duration of 27 months)
description
Investigator assessed maintenance PFS was defined as the time from Cycle 1 Day 1 of the maintenance phase to the date of the first documentation of PD or death due to any cause, whichever occurs first. It was defined, for participants who proceeded to maintenance phase and who did not have disease progression by investigator during the chemotherapy phase. As per RECIST version 1.1, PD was defined as at least a 20% increase in the sum of diameters of target lesions, taking as reference the smallest sum on study (this included the baseline sum if that is the smallest on study). In addition to the relative increase of 20%, the sum must have also demonstrated an absolute increase of at least 5 mm. The appearance of one or more new lesions was also considered progression. Analysis was performed using Kaplan-Meier method
measure
Maintenance Progression-Free Survival (PFS) as Assessed by Investigator
time Frame
From Day 1 of Cycle 1 (42 days) of maintenance phase to progression of disease or death, whichever occurred first (maximum duration of 27 months)
description
pCR was defined (for neoadjuvant participants who underwent interval debulking surgery \[IDS\]), as the chemotherapy response score 3 (CSR3), based on a study by Bohm et al, 2015. CSR3 was defined as complete or near-complete response with no residual tumor or minimal irregularly scattered tumor foci seen as individual cells, cell groups, or nodules up to 2 mm. Complete or near-complete response was defined as complete or near-complete microscopic disappearance of invasive tumor/ residual disease.
measure
Percentage of Participants With Pathological Complete Response (pCR)
time Frame
Baseline to progression of disease or discontinuation from the study or death, whichever occurred first (maximum duration of 27 months)
description
PFS2 was defined as time (in months) from the date of randomization to the start of second subsequent treatment after first documentation of PD, or death from any cause, whichever occurred first. Progression as per RECIST version 1.1, was defined as at least a 20% increase in the sum of diameters of target lesions, taking as reference the smallest sum on study (this included the baseline sum if that is the smallest on study). In addition to the relative increase of 20%, the sum must have also demonstrated an absolute increase of at least 5 mm. The appearance of one or more new lesions was also considered progression. Analysis was performed using Kaplan-Meier method.
measure
Progression-Free Survival 2 (PFS2)
time Frame
Baseline up to start of second subsequent treatment after first PD or discontinuation from study or death, which ever occured first (maximum duration of 27 months)
description
PFS by GCIG was assessed by both RECIST 1.1 and cancer antigen 125 (CA-125). It was defined as time from randomization to first documentation of disease progression (PD) or death, whichever occurred first. As per RECIST 1.1, PD: greater than or equal to (\>=) 20 % increase in the sum of diameters of target lesions, taking as reference the smallest sum on study with absolute increase \>= 5 millimeters. PD based on serum CA-125 was defined as (i) participants with elevated CA-125 pretreatment and normalization of CA-125, (ii) participants with CA-125 in the reference range before treatment; (i) and (ii) must have showed CA-125 \>= 2 times the upper limit of the reference range on 2 occasions \>= 1 week apart, or (iii) participants with elevated CA-125 before treatment, which never normalized, showed CA-125 \>= 2 times the nadir value on 2 occasions \>= 1 week apart. Censoring date for PFS by GCIG was the latest of the censoring dates for PFS by RECIST 1.1 and PFS by CA-125.
measure
Progression-Free Survival (PFS) as Assessed by Gynecological Cancer Intergroup (GCIG) Criteria
time Frame
Baseline until disease progression by GCIG criteria or start of new anti-cancer therapy or discontinuation from the study or death, whichever occurred first (maximum duration of 27 months)
description
An AE was any untoward medical occurrence in a participant who received study drug without regard to possibility of causal relationship. As per NCI-CTCAE version 4.03, Grade 1: asymptomatic or mild symptoms, clinical or diagnostic observations only, intervention not indicated; Grade 2: moderate, minimal, local or noninvasive intervention indicated, limiting age-appropriate instrumental activities of daily life (ADL); Grade 3: severe or medically significant but not immediately life-threatening, hospitalization or prolongation of existing hospitalization indicated, disabling, limiting self-care ADL; Grade 4: life-threatening consequence, urgent intervention indicated; Grade 5: death related to AE. Treatment-emergent events are events between first dose of study drug and up to 36 months that were absent before treatment or that worsened relative to pretreatment state.
measure
Number of Participants With Treatment-Emergent Adverse Events (AEs) Graded Based on, National Cancer Institute Common Terminology Criteria (NCI-CTCAE), Version 4.03
time Frame
Baseline to discontinuation from the study or death, whichever occurred first (maximum duration of 36 months)

Full study description

brief Summary: This is a Phase 3, open-label, international, multi-center, efficacy, and safety study of avelumab in combination with and/or following platinum-based chemotherapy. Eligible patients must have previously untreated, histologically confirmed Stage III-IV epithelial ovarian (EOC), fallopian tube cancer (FTC), or primary peritoneal cancer (PPC) and be candidates for platinum-based chemotherapy. The primary purpose of the study is to demonstrate if avelumab given as single agent in the maintenance setting following frontline chemotherapy or in combination with carboplatin/paclitaxel is superior to platinum-based chemotherapy alone followed by observation in this population of newly diagnosed ovarian cancer patients.

Source references

references

citation
Monk BJ, Colombo N, Oza AM, Fujiwara K, Birrer MJ, Randall L, Poddubskaya EV, Scambia G, Shparyk YV, Lim MC, Bhoola SM, Sohn J, Yonemori K, Stewart RA, Zhang X, Perkins Smith J, Linn C, Ledermann JA. Chemotherapy with or without avelumab followed by avelumab maintenance versus chemotherapy alone in patients with previously untreated epithelial ovarian cancer (JAVELIN Ovarian 100): an open-label, randomised, phase 3 trial. Lancet Oncol. 2021 Sep;22(9):1275-1289. doi: 10.1016/S1470-2045(21)00342-9. Epub 2021 Aug 4.
pmid
34363762
type
DERIVED